This SDAC will provide me with the additional training and skills I need to become an independent investigator in the genetics of bipolar affective disorder (BPAD). The proposed career development plan aims to extensively develop my skills in molecular genetic methods. Courses and workshops in genetic epidemiology, linkage, and association analysis will complement laboratory training in molecular genetic techniques. J. Raymond DePaulo, Kirby Smith, and Douglas C. Wallace will serve as preceptors. The training program will be enhanced by a research plan aimed at investigating the potential role that loci located on chromosome 18 and within the mitochondrial genome play in the etiology of BPAD. Both regions are implicated by prior data as potential sites of BPAD susceptibility loci. I plan to examine a defined region on chromosome 18 for microsatellite marker alleles in linkage disequilibrium with bipolar I disorder (BPI). The region I will examine has been implicated by two independent genetic linkage studies. As a parallel aim, I will screen the 16.5 kilobase mitochondrial genome for polymorphisms associated with (BPI). Both projects are types of family-based association studies. The sample will consist of BPI probands and their relatives already ascertained and clinically evaluated at Johns Hopkins. This integrated career development and research program will provide me with the expertise essential for fulfilling my long-term career goal of identifying and studying genes that play an important role in BPAD and other major mental illnesses.